bioRxiv Subject Collection: Neuroscience's Journal
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Tuesday, December 5th, 2023
| Time |
Event |
| 9:46a |
Spatially resolved molecular and cellular atlas of the mouse brain
A comprehensive atlas of genes, cell types, and their spatial distribution across a whole mammalian brain is fundamental for understanding function of the brain. Here, using snRNA-seq and Stereo-seq techniques, we generated a mouse brain atlas with spatial information for 308 cell clusters with single-cell resolution involving over 6 million cells as well as for 29,655 genes. We have identified new astrocyte clusters, and demonstrated that distinct cell clusters exhibit preference for cortical subregions. In addition, we identified 155 genes exhibiting regional specificity in the brainstem, and 513 long non-coding RNA exhibited regional specificity in the adult brain. Parcellation of brain regions based on spatial transcriptomic information showed large overlap with that by traditional method. Furthermore, we have uncovered 411 transcription factor regulons with spatiotemporal specificity during development. Thus, our study has discovered genes and regulon with spatiotemporal specificity, and provided a high-resolution spatial transcriptomic atlas of the mouse brain. | | 11:46a |
When Age Tips the Balance: a Dual Mechanism Affecting Hemispheric Specialization for Language
Aging engenders neuroadaptations, generally reducing specificity and selectivity in functional brain responses. Our investigation delves into the functional specialization of brain hemispheres within language-related networks across adulthood. In a cohort of 728 healthy adults spanning ages 18 to 88, we modeled the trajectories of inter-hemispheric asymmetry concerning the principal functional gradient across 37 homotopic regions of interest (hROIs) of an extensive language network known as the Language-and-Memory Network. Our findings reveal that over two-thirds of Language-and-Memory Network hROIs undergo asymmetry changes with age, falling into two main clusters. The first cluster evolves from left-sided specialization to right-sided tendencies, while the second cluster transitions from right-sided asymmetry to left-hemisphere dominance. These reversed asymmetry shifts manifest around midlife, occurring after age 50, and are associated with poorer language production performance. Our results provide valuable insights into the influence of functional brain asymmetries on language proficiency and present a dynamic perspective on brain plasticity during the typical aging process. | | 11:46a |
Cross-linguistic and acoustic-driven effects on multiscale neural synchrony to stress rhythms
We investigated how neural oscillations code the hierarchical nature of stress rhythms in speech and how stress processing varies with language experience. By measuring phase synchrony of multilevel EEG-acoustic tracking and intra-brain cross-frequency coupling, we show the encoding of stress involves different neural signatures (delta rhythms = stress foot rate; theta rhythms = syllable rate), is stronger for amplitude vs. duration stress cues, and induces nested delta-theta coherence mirroring the stress-syllable hierarchy in speech. Only native English, but not Mandarin, speakers exhibited enhanced neural entrainment at central stress (2 Hz) and syllable (4 Hz) rates intrinsic to natural English. English individuals with superior cortical-stress tracking capabilities also displayed stronger neural hierarchical coherence, highlighting a nuanced interplay between internal nesting of brain rhythms and external entrainment rooted in language-specific speech rhythms. Our cross-language findings reveal brain-speech synchronization is not purely a 'bottom-up' but benefits from 'top-down' processing from listeners` language-specific experience. | | 11:46a |
Neurophysiology of perceptual decision-making and its alterations in attention deficit hyperactivity disorder (ADHD)
ADHD is a prevalent neurodevelopmental disorder associated with adverse outcomes and significant social and economic cost. However, efforts to develop a more detailed understanding of the neuropsychology of ADHD are complicated by the diversity of interindividual presentation and the inability of current clinical tests to distinguish between its sensory, attentional, arousal or motoric contributions. Identifying objective methods that can decompose the clinical heterogeneity of ADHD is a long-held goal that will advance our understanding of aetiological processes and aid the development of personalised treatment approaches. Here, we examine key neuropsychological components of ADHD with an electrophysiological (EEG) decision making paradigm capable of isolating distinct neural signals of several key information processing stages necessary for sensory-guided actions from initial sensory processing to motor responses. We show that compared to typically developing children, children with ADHD display slower and less accurate behavioural performance driven by the atypical dynamics of discrete electrophysiological signatures of attentional allocation, the accumulation of sensory evidence, and strategic adjustments reflecting urgency of response. These findings offer an integrated account of impairments in ADHD and establish neural signals that can serve as critical guidance in constructing or constraining mechanistic accounts in future research, as well as in ADHD diagnosis and treatment tailoring. | | 11:46a |
MARK1 regulates dendritic spine morphogenesis and cognitive functions in vivo
Dendritic spines play a pivotal role in synaptic communication and are crucial for learning and memory processes. Abnormalities in spine morphology and plasticity are observed in neurodevelopmental and neuropsychiatric disorders, yet the underlying signaling mechanisms remain poorly understood. The microtubule affinity regulating kinase 1 (MARK1) has been implicated in neurodevelopmental disorders, and the MARK1 gene shows accelerated evolution in the human lineage suggesting a role in cognition. However, the in vivo role of MARK1 in synaptogenesis and cognitive functions remains unknown. Here we show that forebrain-specific conditional knockout (cKO) of Mark1 causes defects in dendritic spine morphogenesis in hippocampal CA1 pyramidal neurons with a significant reduction in spine density. In addition, we found that MARK1 cKO mice show defects in spatial learning in the Morris Water Maze and reduced anxiety-like behaviors in the Elevated Plus Maze. Furthermore, we found loss of MARK1 causes synaptic accumulation of GKAP and GluR2. Taken together, our data show a novel role for MARK1 in regulating dendritic spine morphogenesis and cognitive functions in vivo. | | 11:46a |
Higher-order connectomics of human brain function reveals local topological signatures of task decoding, individual identification, and behavior
Traditional models of human brain activity often represent it as a network of pairwise interactions between brain regions. Going beyond this limitation, recent approaches have been proposed to infer higher-order interactions from temporal brain signals involving three or more regions. However, to this day it remains unclear whether methods based on inferred higher-order interactions outperform traditional pairwise ones for the analysis of fMRI data. To address this question, we conducted a comprehensive analysis using fMRI time series of 100 unrelated subjects from the Human Connectome Project. We show that higher-order approaches greatly enhance our ability to decode dynamically between various tasks, to improve the individual identification of unimodal and transmodal functional subsystems, and to strengthen significantly the associations between brain activity and behavior. Overall, our approach sheds new light on the higher-order organization of fMRI time series, improving the characterization of dynamic group dependencies in rest and tasks, and revealing a vast space of unexplored structures within human functional brain data, which may remain hidden when using traditional pairwise approaches. | | 6:19p |
Satellite glial GPR37L1 regulates maresin and potassium channel signaling for pain control
G protein coupled receptor 37-like 1 (GPR37L1) is an orphan GPCR and its function remains largely unknown. Here we report that GPR37L1 transcript is highly expressed compared to all known GPCRs in mouse and human dorsal root ganglia (DRGs) and selectively expressed in satellite glial cells (SGCs). Peripheral neuropathy following diabetes and chemotherapy by streptozotocin and paclitaxel resulted in downregulations of surface GPR37L1 in mouse and human DRGs. Transgenic mice with Gpr37l1 deficiency exhibited impaired resolution of neuropathic pain symptom (mechanical allodynia), whereas overexpression of Gpr37l1 in mouse DRGs can reverse neuropathic pain. Notably, GPR37L1 is co-expressed and coupled with potassium channels in SGCs. We found striking species differences in potassium channel expression in SGCs, with predominant expression of KCNJ10 and KCNJ3 in mouse and human SGCs, respectively. GPR37L1 regulates the surface expression and function of KCNJ10 and KCNJ3. We identified the pro-resolving lipid mediator maresin 1 (MaR1) as a GPR37L1 ligand. MaR1 increases KCNJ10/KCNJ3-mediated potassium influx in SGCs via GPR37L1. MaR1 protected chemotherapy-induced suppression of KCNJ13/KCNJ10 expression and function in SGCs. Finally, genetic analysis revealed that the GPR37L1-E296K variant is associated with increased chronic pain risk by destabilizing the protein. Thus, GPR37L1 in SGCs offers a new target for neuropathy protection and pain control. | | 11:18p |
Revisiting the Kuleshov effect with authentic films: A behavioral and fMRI study
As a fundamental film theory, montage theory posits that film editing significantly influences the viewer's perception. The Kuleshov effect, a central concept in montage theory, proposes that the emotional interpretation of neutral facial expressions is influenced by the accompanying emotional scene in a face-scene-face sequence. However, concerns persist regarding the validity of previous studies, often employing inauthentic film materials like static images, leaving the question of its existence in authentic films unanswered. This study addresses these concerns by utilizing authentic films in two experiments. In Experiment 1, multiple film clips were captured under the guidance of a professional film director and seamlessly integrated into authentic film sequences. A total of 59 participants viewed these face-scene-face film sequences and were tasked with rating the valence of neutral faces. The findings revealed that the interpretation of emotion in neutral faces is significantly influenced by the accompanying fearful or happy scene, eliciting perceptions of negative or positive emotion from the neutral face. These results affirm the existence of the Kuleshov effect within authentic film sequences. In Experiment 2, 31 participants engaged in a similar task under functional magnetic resonance imaging (fMRI). The results revealed neural correlates supporting the existence of the Kuleshov effect at a neural level. These correlates include the cuneus, precuneus, hippocampus, parahippocampal gyrus, post cingulate gyrus, orbitofrontal cortex, fusiform gyrus, and insula. These findings also underscore the contextual framing inherent in the Kuleshov effect. By seamlessly integrating film theory and cognitive neuroscience experiments, this comprehensive study provides robust evidence supporting the existence of the Kuleshov effect. It significantly enhances our understanding of film editing and its profound impact on viewers' perception. | | 11:18p |
Increased susceptibility for pathogenesis of post-traumatic epilepsy in offspring exposed to deltamethrin during gestation and ameliorative effects of dietary curcumin
Deltamethrin (DLT) is a most potent and widely used pesticide that does not cross Blood Brain Barrier (BBB) in adults. While it considered as safe, its lipophilic properties makes it a neurotoxic substance specially in early stages of brain development. It has shown neurotoxic effects on the brain by hyper-excitation of neurons. Epilepsy is a neurological disorder with recurring seizures where epileptogenesis occurs due to hyperexcitation of neurons. In various kinds of epilepsy, post-traumatic epilepsy (PTE) is a common epilepsy in children due to traumatic brain injury (TBI). PTE, however reportedly alleviated by curcumin in rats. Therefore, in the current study, we assessed the effect of gestational DLT exposure on the severity of PTE. The pregnant rats were injected with 0.75mg/kg-b/w of DLT dissolved in 1% DMSO each day of gestation between days 7-15. Epilepsy was induced four months postnatally, and curcumin was orally administered by oral gavage. ECoG, behavioral tests, Golgi Staining, immunofluorescence, and immunohistochemistry was performed to assess the pathogenesis, severity of epilepsy, and mitigating effects of curcumin. The results indicated the neurotoxic effects of DLT by raising the severity of seizures in an electrophysiological and behavioral manner. PTE decreased the dendritic branching and arborization. Sodium channel overexpression is an important reason for the hyperexcitation of neurons during the pathogenesis of epilepsy. DLT enhanced the increase in expression of both sodium channel subunits NaV1.1 and NaV1.6 during epileptogenesis. Similarly, synaptic markers PSD95 and SYP decreased. Astrocytic and microglial activation increased during pathogenesis of PTE. The antiepileptic effects of curcumin alleviated the effects on electrobehavioral response, neuronal arborization, and levels of NaVs, PSD95, SYP, GFAP and Iba1 in epilepsy. However, DLT raised the severity and susceptibility of epilepsy and decreased the antiepileptic effects on gestationally DLT-exposed epileptic animals. Our result demonstrates the gestational neurotoxic exposure of DLT increased the severity and susceptibility for PTE while decreasing the antiepileptic effects of curcumin. | | 11:19p |
Imaging neuronal voltage beyond the scattering limit
Voltage imaging is a promising technique for high-speed recording of neuronal population activity. However, tissue scattering severely limits its application in dense neuronal populations. Here, we adopted the principle of localization microscopy, a technique that enables super-resolution imaging of single-molecules, to resolve dense neuronal activities in vivo. Leveraging the sparse activation of neurons during action potentials (APs), we precisely localize the fluorescence change associated with each AP, creating a super-resolution image of neuronal activities. This approach, termed Activity Localization Imaging (ALI), identifies overlapping neurons and separates their activities with over 10-fold greater precision than what tissue scattering permits. Using ALI, we simultaneously recorded over a hundred densely-labeled CA1 neurons, creating a map of hippocampal theta oscillation at single-cell and single-cycle resolution. |
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